Amnesia after Repeated Head Impact Is Caused by Impaired Synaptic Plasticity in the Memory Engram

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Cognitive Deficits

Background:

• Subconcussive head impacts are linked to cognitive deficits.
• High-frequency head impacts (HFHI) cause chronic cognitive deficits via synaptic changes.

Purpose of the Study:

• Investigate mechanisms of HFHI-induced memory decline.
• Examine synaptic plasticity in memory engrams after HFHI.

Main Methods:

• Used TRAP2/Ai32 transgenic mice to visualize and manipulate memory engrams.
• Labeled fear memory engrams in mice exposed to sham or HFHI.
• Assessed memory retrieval and synaptic plasticity (AMPA:NMDA ratio, tau, spine volume).
• Utilized optogenetics to artificially activate engrams.

Main Results:

• HFHI mice failed to retrieve fearful memories compared to sham mice.
• Sham mice showed synaptic plasticity in hippocampal engram neurons; HFHI mice did not.
• HFHI impaired engram network activation, causing retrograde amnesia.
• Optogenetic stimulation of engrams restored memory recall identically in both groups.

Conclusions:

• HFHI-induced cognitive impairment results from impaired synaptic plasticity, not neuronal loss.
• Memory deficits are linked to deficiencies in engram network activation.
• Targeting synaptic plasticity offers therapeutic potential for memory impairments from repeated head impacts.